View clinical trials related to Malignant Melanoma Stage III.
Filter by:This is an international (Australia, Europe, and USA) open-label two-arm randomized phase 3 trial including 420 stage III (≤3 resectable in-transit metastases allowed) cutaneous or unknown primary melanoma patients. Patients will be randomized 1:1 to receive either 2 cycles of neoadjuvant ipilimumab 80 mg + nivolumab 240 mg every 3 weeks followed by a total lymph node dissection (TLND) and, if applicable, resection of in-transit metastases (arm A) versus standard upfront TLND +/- resection of in-transit metastases followed by 12 cycles adjuvant nivolumab 480 mg every 4 weeks (arm B). Patients with a pathologic partial or non-response in arm A will also receive adjuvant nivolumab 480 mg every 4 weeks for 46 weeks (11 cycles). In case of BRAF V600E/K mutation-positivity, patients from arm A with a pathologic partial or non-response (>10% viable tumor) will be treated with adjuvant dabrafenib plus trametinib for 46 weeks. Patients will be treated in the study in both arms until melanoma progression to irresectable stage III or stage IV disease, disease recurrence, unacceptable toxicity, subject withdrawal of consent or until end of study treatment. An interim analysis will be performed after 60 events have occurred. The data safety monitory board (DSMB) will be ad hoc consulted when unexpected toxicities are reported. Patients will be followed by 12 weekly CT scans until end of year 3 and then until year 5 according to the institute's standards.
Aim of the study is to investigate the effect of Fecal Microbiota Transplantation (FMT) and Checkpoint Inhibitor (CI) re-challenge in prior CI refractory patients on Progression free survival (PFS) and tumor using donor stool of former malignant melanoma patients, who have been in remission due to CI treatment for at least 1 year.
DONIMI is a phase 1b trial testing the combination of domatinostat + nivolumab or nivolumab monotherapy in IFN-gamma signature high patients and of domatinostat + nivolumab or domatinostat + nivolumab + ipilimumab in IFN-gamma signature low patients with de-novo or recurrent macroscopic stage III cutaneous or unknown primary melanoma. The trial will include 45 stage III cutaneous or unknown primary melanoma patients with RECIST 1.1 measurable de-novo or recurrent disease (short axis lymph node metastasis ≥1.5cm). NanoString IFN-gamma signature high patients will be randomized to be treated pre-surgically for 6 weeks with nivolumab (arm A; 10 patients) or domatinostat + nivolumab (arm B; 10 patients). IFN-gamma signature low patients will be randomized to be treated pre-surgically for 6 weeks with domatinostat + nivolumab (arm C; 10 patients) or domatinostat + nivolumab + ipilimumab (arm D; 15 patients). Patients will be stratified according to center. Post-surgery (starting at week 12), the patients will start with adjuvant nivolumab or pembrolizumab for 52 weeks according to institute's standard. BRAF V600E/K mutation positive patients with no pathologic response after neoadjuvant therapy may also receive adjuvant BRAF + MEK inhibition if commercially available and according to the patient's and the treating physician's decision. Follow-up after the adjuvant therapy will be for 2 years, according to the institutes' standard. Toxicity and pathologic response rates will be descriptive. In case of 2/5 or 4/10 patients not undergoing their lymph node dissection at week 6 +/- 1 week due to treatment related toxicity, this arm will be declared unfeasible.
The main objective of this project is to perform a longitudinal monitoring of BRAF and NRAS cell-free DNA in a large cohort of metastatic melanomas patients before treatment and during the follow-up. Results will be compared with clinical data as imaging (based on RECIST criteria) and the activity of lactate dehydrogenase in serum (LDH).
This is an open-label three-arm phase 2 trial (including a Simon stage 2 design) consisting of 90 stage III melanoma patients randomized 1:1:1 to receive either 2 courses 3 mg/kg ipilimumab + 1 mg/kg nivolumab every 3 weeks (Arm A), 2 courses 1 mg/kg ipilimumab + 3 mg/kg nivolumab every 3 weeks (Arm B), or 2 courses ipilimumab 3 mg/kg, directly followed by 2 courses nivolumab 3 mg/kg every 2 weeks (Arm C). All three treatment arms are applied prior to surgery at week 6, 30 patients per arm. Patients will be stratified according to treatment center. An interim analysis will be performed after 13 patients have been included in each arm, thus in total 39 patients have been included. PRADO extension cohort The trial will enroll in total about 100-110 melanoma patients with macroscopic stage III disease (RECIST measurable disease); inclusion will stop when 50 patients have achieved a pCR or pnCR. All patients will be treated (after marker placement into the largest lymph node metastasis) with the winner combination identified in the first part of the OpACIN-neo study which is 2 courses ipilimumab 1mg/kg + nivolumab 3mg/kg, q3wks. After 6 weeks of treatment, the patients will undergo only surgical resection of the marked index lymph node. Thereafter subsequent surgery and adjuvant therapy will be performed according to the achieved pathologic response.
This is an open label, 2-arm, 1-stage, randomized controlled phase II study in patients with AJCC stage IIIB/C & -IV melanoma. At baseline tumor assessment (using total body FDG-PET/CT), patients should be free from measurable tumor lesions (according to RECISTv1.1 definitions) following prior local therapy (e.g. following surgical resection, isolated limb perfusion, radiofrequency ablation, cryotherapy, radiotherapy, electrochemotherapy, …). Patients should not have symptomatic non-measurable tumor lesions (e.g. bone metastasis, or pleural effusion), and lesions treated by prior local therapy should be free from progression. Patients should not have received any prior systemic therapy (non-experimental or experimental).
The CTLA-4 blocking monoclonal antibody ipilimumab (MDX-010, BMS-734016), has demonstrated anti-tumor activity in a subgroup of patients with Stage III (unresectable) or Stage IV melanoma (measurable per modified WHO criteria), who have received prior treatment with any regimen (non-experimental or experimental), except a CD-137 agonist or a CTLA4 inhibitor or agonist and relapsed, failed to respond (CR or PR) or did not tolerate that regimen (Wolchok, Neyns et al. 2009; O'Day, Maio et al. 2010). Ipilimumab exerts its therapeutic effect presumably by activating T-lymphocytes that infiltrate the tumor mass to destroy the malignant cells by mechanisms of cytotoxic cellular interaction. Autologous TriMix-DC vaccine can induce a T-cell repertoire that recognizes in a HLA-restricted way the melanoma associated antigens MAGE-A3, MAGE-C2, tyrosinase and gp100. Administration of ipilimumab together with TriMix-DC vaccine therapy may be a more effective treatment for patients with advanced melanoma as compared to either modality alone.
The purpose of the study is to gather data on feasibility as well as immune and clinical efficacy of of a dendritic cell vaccine using IL15 in patients with resected stage III or stage IV melanoma